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Earlier effect of alendronate in mouse metaphyseal versus diaphyseal bone healing
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
2016 (English)In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527XArticle in journal (Refereed) Epub ahead of print
Abstract [en]

Healing of injured cancellous bone is characterized by a transient stage of rapid bone formation throughout the traumatized bone volume, often followed by similarly rapid resorption. This is different from the slower diaphyseal healing via an external callus. We, therefore, hypothesized that antiresorptive treatment might have an earlier positive effect in cancellous bone healing than in diaphyseal fractures. One hundred and twenty-three male C57bl6 mice received either an internally stabilized diaphyseal osteotomy of the femur or a screw inserted into the tibial metaphysis. The mice were randomized to daily alendronate injections (200 μg/kg/day), or control injections, and killed for mechanical testing after 14, 21, or 28 days. The hypothesis was tested by a three-way Anova (time, site, and drug). The ultimate force was increased by bisphosphonate treatment in both models. There was a significant interaction between time, site, and drug (p < 0.001) so that the full positive effect of alendronate was evident in the metaphysis at 14 days, but first after 28 days in the diaphysis. While the early effect in the metaphysis might be translated into earlier healing, the late effect in the diaphysis was due to delayed remodeling of the callus, which might have less clinical importance. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

Place, publisher, year, edition, pages
John Wiley & Sons, 2016.
Keyword [en]
fracture, bisphosphonate, metaphysis, cancellous bone, trabecular bone, alendronate
National Category
Clinical Medicine Orthopedics Nursing
URN: urn:nbn:se:liu:diva-130921DOI: 10.1002/jor.23316PubMedID: 27233101OAI: diva2:956687
Swedish Research CouncilLinköpings universitetÖstergötland County CouncilEU, FP7, Seventh Framework Programme
Available from: 2016-08-31 Created: 2016-08-31 Last updated: 2016-09-05Bibliographically approved
In thesis
1. Metaphyseal Fracture Healing
Open this publication in new window or tab >>Metaphyseal Fracture Healing
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Most of what is known about fracture healing comes from studies of shaft fractures in long bones. In contrast, patients more often have fractures closer to the ends (metaphyses). Here most bone tissue has a spongy, cancellous structure different from the compact bone of the shaft. There is an increasing awareness that metaphyseal fractures heal differently. However, the more easily studied shaft healing has usually been considered as good enough representative for fracture healing in general.

My work shows that the biology of metaphyseal healing is more different from shaft healing than was previously known and that this has implications on the effect of various commonly prescribed drugs.

First we studied biopsies of healing cancellous bone collected from human donors. We found that the most abundant new bone formation occurred freely in the marrow rather than on the surface of old trabeculae, as described in most literature. There was little cartilage, indicating that the dominant bone formation process is mostly membranous in nature. This is a contrast to the ample cartilage formation commonly found in the well-characterized shaft fracture models.

Next we characterized a model that allows for mechanical quantification of regenerating cancellous bone. By contrasting this cancellous healing model with the standard shaft healing model we could demonstrate that the NSAID indomethacin, the glucocorticoid dexamethasone, and the bisphosphonate alendronate all had different effects on the mechanical quality of bone regeneration in shaft and metaphysis; while anti-inflammatory drugs strongly impaired shaft healing, metaphyseal healing was not similarly affected. Alendronate had a positive effect on both models, though the effect was strongest in the metaphyseal model. Taken together these differences shed some light as to the differences in healing biology.

The last step (within the boundaries of this thesis) was a characterization of how healing in cortical and cancellous bone differs in terms of immune cell involvement. We could find little difference between the two bone types day 3. However, day 5 an increase in the number of granulocytes could be noted in the cancellous bone while the cortical bone had a higher number of lymphocytes.

To conclude, this work furthers our understanding of how metaphyseal healing differs from shaft healing. It has clinical implications as it motivates an increased attention to the site of fracture while contemplating treatment. I hope this thesis can be read as an argument for increased interest in metaphyseal fracture healing.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 22 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1502
National Category
Other Clinical Medicine Orthopedics Nursing
urn:nbn:se:liu:diva-126148 (URN)10.3384/diss.diva-126148 (DOI)978-91-7685-865-3 (Print) (ISBN)
Public defence
2016-04-26, Nils Holger salen, ing 71 pl 8, Campus US, Linköping, 14:00 (English)
Available from: 2016-03-15 Created: 2016-03-15 Last updated: 2016-08-31Bibliographically approved

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Sandberg, OlofBernhardsson, MagnusAspenberg, Per
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